摘要
目的观察大剂量螺内酯对自发性高血压大鼠（SHR）肾脏纤维化的影响。方法8周龄的雄性SHR24只随机分为低剂量和大剂量螺内酯干预组[分别为20和100mg·kg^-1·d^-1螺内酯灌胃]和高血压对照组，同时设同源正常对照组京都大鼠（WKY）8只。干预8周，检测收缩压、尿蛋白、血白蛋白、钾、钠、Scr和肾组织及血浆醛固酮水平。肾组织切片分别行HE和Masson染色，以评价肾小球损伤及肾小球内胶原沉积情况。免疫组化SABC法检测肾组织TGF—β1和醛固酮受体蛋白表达。RT—PCR检测肾组织TGF—β1和醛固酮受体mRNA水平。结果与高血压组大鼠相比，低剂量螺内酯干预后，尿蛋白减少（P〈0．05），血白蛋白升高（P〈0．05），血浆和肾组织醛固酮水平降低，但差异无统计学意义；大剂量螺内酯干预后，血压没有显著改变，尿蛋白显著升高[（27．3±4．5）比（24．5±3．2）mg／d，P〈0．05]，血白蛋白显著减少[（20．2±4．2）比（22．7±3．5）g／L，P〈0．05]，血浆和肾组织醛固酮水平显著升高[肾组织（28．3±1．5）比（22．2±0．6）ng／g，P〈0．05]。与高血压组比较，低剂量螺内酯干预后，蛋白管型增多、管周炎性细胞浸润均减少（P〈0．05）；大剂量螺内酯干预后，蛋白管型、小管扩张加重，管周炎性细胞浸润明显增多（P〈0．05），肾小球内胶原形成亦明显增多（P〈0．05）。与高血压组大鼠比较，低剂量螺内酯干预后，肾组织醛固酮受体mRNA和蛋白表达均无显著改变，TGF—β1 mRNA和蛋白的表达显著减少（P〈0．05）；大剂量螺内酯干预后，肾组织醛固酮受体及TGF—β1 mRNA和蛋白的表达均显著升高（P〈0．05）。结论大剂量螺内酯可以加重高血压肾脏纤维化，可能是通过上调醛固酮及其受体表达实现的。
Objective To investigate the effect of large dosage of spironolactone on renal fibrosis in spontaneously hypertensive rats. Methods Twenty-four 8-week aged spontaneously hypertensive rats were divided into low and large dosage of spironolactone group and control group. Eight normal Wistar-Kyoto rats were as normal group. Low and large dosage groups were given spironolactone 20 mg ·kg^-1 ·d^-1 and 100 mg·kg^-1 ·d^-1 for 8 weeks. Then systolic blood pressure, proteiuria, albumin, K^＋,Na^＋, Scr, the aldosterone level of kidney tissue and plasma were measured. Renal tissue sections were stained by HE and Masson for evaluating glomerular injury and collagen deposition. The protein expression of TGF-β1 and aldosterone receptor in renal tissue were detected by immunohistochemical SABC method, and the mRNA levels were detected by RT-PCR. Results Compared to the controls, in low dosage of spironolactone group, urinary protein decreased （P〈0.05）, serum albumin increased （P〈0.05）, plasma and renal tissue aldosterone levels decreased, without significant diffeence. In large dosage of spironolactone group, blood pressure had no significant change, whereas the levels of urinary protein[（27.3±4.5） vs （24.5±3.2） mg/d] as well as plasma and renal tissue aldosterone [（28.3±1.5） vs （22.2±0.6） ng/g] increased significantly （P〈 0.05）, and serum albumin [（20.2±4.2） vs （22.7±3.5） g/L] decreased significantly （P〈0.05）. Compared to the controls, in low dosage of spironolactone group, protein cast and inflammatory cells infiltration around tubules reduced （P〈0.05）; the renal tissue aldosterone receptor mRNA and protein expression did not change significantly, TGF-β1 mRNA and protein expression reduced significantly （P〈0.05）. In high-dose spironolactone group, protein cast and inflammatory cells infiltration around tubules increased significantly （P 〈0.05）, and glomerular collagen formation also increased significantly （P〈0.05）; the renal tissue aldoste
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2008年第1期40-45,共6页
Chinese Journal of Nephrology
基金
广东省自然科学基金（05001702）
关键词
醛固酮
螺内酯
高血压
纤维化
Aldosterone
Spironolactone
Hypertension
Fibrosis
